Vertebrates have two basic immune responses: humoral or cellular. Humoral immunity is provided by the special class of cells produced by B lymphocytes. These cells produce antibodies which circulate in the blood and lymphatic fluid. On the other hand, cell mediated immunity is provided by the T cells of the lymphatic system.
The cellular immune response is particularly effective against fungi, parasites, intracellular viral infections, cancer cells and foreign matter, whereas the humoral response primarily defends against the extracellular phases of bacterial and viral infections.
Containment of antigen at its point of entry is accomplished by walling off the area by local inflammation. Acute inflammation is characterized by the influx of plasma proteins and polymorphonuclear leukocytes. Chronic inflammation is characterized by the infiltration of T-lymphocytes and macrophages. When acute (antibody induced) and chronic (T cell induced) inflammations occur in the o skin, they are called immediate and delayed type hypersensitivity reactions respectively. ITH peaks at 24 hours, and subsides in 48 hours DTH appears in 24-48 hours and peaks at 48-72 hours. The subset of T cells involved in DTH reactions are called here DTH-Effector cells.
Epiglycanin (epi) is the major cell surface glycoprotein produced by the mammary adenocarcinoma transplantable cell line TA3Ha. Friberg, Jr., J.N.C.I., 48:1463 (1972); Codington, et al., Canc. Res., 43:4373 (1983). The TA3Ha carcinoma cells are covered by a mucin-like glycocalix composed mainly of epiglycanin. Codington, et al., J.N.C.I., 60:811 (1978); Miller, et al., J.N.C.I., 68:981 (1982). Epi is mainly carbohydrate in composition, and expresses multiple T and Tn determinants. T and Tn are general carcinoma autoantigens. Springer, Science, 224:1198 (1984).
Synthetic T and Tn antigens have been prepared, and used in DTH diagnostics. Lemieux, Ep Appl. 44, 188. However, their therapeutic or prophylactic use has not been disclosed.
Bretscher, Eur. J. Immunol., 9:311-316 (1979) cultured DTH-Effector cells in vitro and injected them with the sensitizing antigen (burro erythrocytes) into the foot pads of mice. We have used cancer-associated, well characterized carbohydrate antigens to sensitize effector cells and have taught a therapeutic use for them.
It is known that tumors may be treated with a mixture of IL-2 and IL-2-activated killer cells. See Fortune, 16-21 (Nov. 25, 1985), reporting on the work of Steven Rosenberg. The problem with the Rosenberg work is that the therapy induces a population of cells known as LAK (lymphokine activated killer) cells. LAK cells are not antigen-specific; therefore normal tissue may be attacked. Also, since the LAK cells are non-specific, relatively large doses of IL-2 are required to induce the required anti-tumor activity. Finally, LAK cells are not thought to confer memory to the immune system. In contrast, DTH effector cells are antigen specific; therefore after stimulation much smaller quantities of lymphokine may be required to induce proliferation. Also because of their specificity, DTH effector cells are less likely to attack self. Moreover, DTH effector cells are though to have memory.